TOXIN PEPTIDE THERAPEUTIC AGENTS

• US 20110045587A1
• Filed: 11/02/2010
• Published: 02/24/2011
• Est. Priority Date: 04/22/2005
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Sullivan, John K., McGivern, Joseph G., Miranda, Leslie P., Nguyen, Hung Q., Walker, Kenneth W., Hu, Shaw-Fen Sylvia, Gegg, Colin V., McDonough, Stefan I.
• Granted Patent: US 8,907,071 B2
• Time in Patent Office: Days
• US Class Current: 435/358
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/43504 from invertebrates
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/55 containing a fusion with a toxin, e.g. diphteria toxin

Abstract

Disclosed is a DNA encoding a composition of matter of the formula

(X¹)_a—(F¹)_d—(X²)_b—(F²)_e—(X³)_c  (I)

and multimers thereof, in which F¹ and F² are half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X¹, X², and X³ are each independently -(L)_f-P-(L)_g-, and f and g are each independently 0 or 1; P is a ShK peptide analog of no more than about 80 amino acid residues in length; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. A DNA encoding the ShK peptide analog is disclosed. Also disclosed are an expression vector comprising the DNA, and a host cell comprising the expression vector.

Claims

1. A DNA encoding a composition of matter for extending the half-life of a polypeptide, of the formula

(X¹)_a—

(F¹)_d—

(X²)_b—

(F²)_e—

(X³)_c

or multimers thereof, wherein;

F¹ and F² are half-life extending moieties selected from;

(i) a human IgG Fc domain or a portion thereof,

(ii) a transthyretin protein domain, and

(iii) a human serum albumin (HSA) protein domain;

and d and e are each independently 0 or 1, provided that at least one of d and e is 1;

X¹, X², and X³ are each independently -(L)_f-P-(L)_g-, and f and g are each independently 0 or 1;

P is a polypeptide of no more than about 80 amino acid residues in length, comprising the amino acid sequence of SEQ ID NO;

914, SEQ ID NO;

915, SEQ ID NO;

916, or SEQ ID NO;

917;

L is a linker; and

a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1.

2. The DNA of claim 1 of a formula selected from

P-(L)_g-F¹,

F¹-(L)_f-P,

P-(L)_g-F¹-(L)_f-P,

F¹-(L)_f-P-(L)_g-F²,

F¹-(L)_f-P-(L)_g-F²-(L)_f-P,

F¹—

F²-(L)_f-P,

P-(L)_g-F¹—

F², and

P-(L)_g-F¹—

F²-(L)_f-P.

3. The DNA of claim 1, wherein F¹ or F², or both, comprises a human IgG Fc domain or a portion thereof.

4. The DNA of claim 3, wherein the human IgG Fc domain comprises a human IgG1 Fc domain.

5. The DNA of claim 4, wherein the human IgG Fc domain comprises a human IgG2 Fc domain.

6. The DNA of claim 1, wherein F¹ and F² are different half-life extending moieties.

7. The DNA of claim 1, wherein claim 1, wherein any f or any g is 1, and L is a peptide linker comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:

79, 84, and 637 through 656.

8. The DNA of claim 1, wherein F¹ or F², or both, comprises a human serum albumin protein domain or a transthyretin protein domain.

9. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:

914.

10. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:

915.

11. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:

916.

12. The DNA of claim 1, wherein P comprises the amino acid sequence of SEQ ID NO:

917.

18. An expression vector comprising the DNA of claim 1 or claim 13.

19. A host cell comprising the expression vector of claim 18.

20. The host cell of claim 19, wherein the cell is a eukaryotic cell.

21. The host cell of claim 20, wherein the cell is a mammalian cell.

22. The host cell of claim 21, wherein the cell is a CHO cell.

23. The host cell of claim 19, wherein the cell is a prokaryotic cell.

24. The host cell of claim 23, wherein the cell is an E. coli cell.

13. A DNA encoding a polypeptide comprising the amino acid sequence of SEQ ID NO:

914, SEQ ID NO;

915, SEQ ID NO;

916, or SEQ ID NO;

917.

14. The DNA of claim 13, wherein the DNA encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:

914.

15. The DNA of claim 13, wherein the DNA encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:

915.

16. The DNA of claim 13, wherein the DNA encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:

916.

17. The DNA of claim 13, wherein the DNA encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:

917.